tbuckley/cabot-search huggingface dataset:
Plasma adiponectin levels and risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction: large-scale observational and Mendelian randomization evidence
Authors: Maria Booth Nielsen, Yunus Çolak, Marianne Benn, Amy Mason, Stephen Burgess, Børge Grønne Nordestgaard
Journal: Cardiovascular Research (2023)

Abstract Aims Adiponectin may play an important protective role in heart failure and associated cardiovascular diseases. We hypothesized that plasma adiponectin is associated observationally and causally, genetically with risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. Methods and results In the Copenhagen General Population Study, we examined 30 045 individuals with plasma adiponectin measurements observationally and 96 903 individuals genetically in one-sample Mendelian randomization analyses using five genetic variants explaining 3% of the variation in plasma adiponectin. In the HERMES, UK Biobank, The Nord-Trøndelag Health Study (HUNT), deCODE, the Michigan Genomics Initiative (MGI), DiscovEHR, and the AFGen consortia, we performed two-sample Mendelian randomization analyses in up to 1 030 836 individuals using 12 genetic variants explaining 14% of the variation in plasma adiponectin. In observational analyses modelled linearly, a 1 unit log-transformed higher plasma adiponectin was associated with a hazard ratio of 1.51 (95% confidence interval: 1.37–1.66) for heart failure, 1.63 (1.50–1.78) for atrial fibrillation, 1.21 (1.03–1.41) for aortic valve stenosis, and 1.03 (0.93–1.14) for myocardial infarction; levels above the median were also associated with an increased risk of myocardial infarction, and non-linear U-shaped associations were more apparent for heart failure, aortic valve stenosis, and myocardial infarction in less-adjusted models. Corresponding genetic, causal risk ratios were 0.92 (0.65–1.29), 0.87 (0.68–1.12), 1.55 (0.87–2.76), and 0.93 (0.67–1.30) in one-sample Mendelian randomization analyses, and no significant associations were seen for non-linear one-sample Mendelian randomization analyses; corresponding causal risk ratios were 0.99 (0.89–1.09), 1.00 (0.92–1.08), 1.01 (0.79–1.28), and 0.99 (0.86–1.13) in two-sample Mendelian randomization analyses, respectively. Conclusion Observationally, elevated plasma adiponectin was associated with an increased risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. However, genetic evidence did not support causality for these associations.
Human platelets do not possess the FcεRI and FcεRII receptors for IgE
Authors: Charles Tacquard, Florian Tupin, Stéphanie Magnenat, Nathalie Brouard, Anita Eckly, Fabienne Proamer, Carine Metz‐Favre, Rodolphe Stenger, Anays Piotin, Frédéric De Blay, Didier Ebo, Jessy Elst, Paul Michel Mertes, Béatrice Hechler
Journal: Allergy (2023)

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Data S1. Figures S1–S2. Table S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Future of Treatment of Adolescents and Young Adults With ALL: A Vision for Collaboration and Equity
Authors: Haley Newman, Stephen P. Hunger
Journal: Journal of Clinical Oncology (2023)

Over the past several decades, survival of children with ALL has improved dramatically with treatment regimens refined through cooperative group trials. Despite aggressive treatment and iterative therapy changes for adolescents and young adults (AYAs), improvement has not been as promising. Comparisons between pediatric and adult clinical trials have consistently demonstrated superior outcomes for AYAs treated on pediatric ALL protocols, leading to the implementation of pediatric-inspired ALL protocols by several groups worldwide and/or expansion of the age limit of pediatric trials to include the full spectrum of the AYA population. Despite these efforts, AYAs in both pediatric and adult settings continue to have inferior survival compared with younger children with ALL. Real-world data suggest that uptake of pediatric-style treatment is variable, and even with identical pediatric-style treatment, AYAs still fare worse than younger children. As we enter an era of immunotherapy and precision medicine for newly diagnosed ALL, now is an opportune time to consider how best to approach future therapy for AYA patients. Comparisons of pediatric and adult treatment approaches and subanalyses of AYA patients will help guide harmonization of treatment. The focus of the next stage of ALL therapy for AYA should not only involve novel treatment approaches but also standardization and optimization of supportive care measures, psychosocial support, adherence interventions, oncofertility treatment, and survivorship care. All these efforts should simultaneously work to address health disparities to ensure that a future of improved outcomes is experienced equitably for all AYA patients.
A unique case of well-differentiated gastric-type adenocarcinoma coexisting with a gastric adenocarcinoma of the fundic gland in a Helicobacter pylori-uninfected stomach
Authors: Zhixia Dong, Shan Wu, Jie Xia, Dongrui Liu, Yueqin Qian, Xinjian Wan
Journal: Endoscopy (2023)
Rheuma-VOR study: optimising healthcare of rheumatic diseases by multiprofessional coordinating centres
Authors: Matthias Dreher, Torsten Witte, Kirsten Hoeper, Gunter Assmann, Fabian Proft, Denis Poddubnyy, Niels Murawski, Konstantinos Triantafyllias, Marlon Grodd, Erika Graf, Urs A Fichtner, Harald Binder, Jan Zeidler, Juliana Rachel Hoeper, Johanna Callhoff, Kirsten Karberg, Anna Trautwein, Dativa Tibyampansha, Leszek Wojnowski, Reinhold E Schmidt, Andreas Schwarting
Journal: Annals of the Rheumatic Diseases (2023)

Early diagnosis of inflammatory arthritis is critical to prevent joint damage and functional incapacities. However, the discrepancy between recommendations of early diagnosis and reality is remarkable. The Rheuma-VOR study aimed to improve the time to diagnosis of patients with early arthritis by coordinating cooperation between primary care physicians, specialists and patients in Germany.
Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001
Authors: Jeremy S. Abramson, M. Lia Palomba, Leo I. Gordon, Matthew Lunning, Michael Wang, Jon Arnason, Enkhtsetseg Purev, David G. Maloney, Charalambos Andreadis, Alison Sehgal, Scott R. Solomon, Nilanjan Ghosh, Christine Dehner, Yeonhee Kim, Ken Ogasawara, Ana Kostic, Tanya Siddiqi
Journal: Blood (2023)
Point mutations in RyR2 Ca2+-binding residues of human cardiomyocytes cause cellular remodelling of cardiac excitation contraction-coupling
Authors: Yanli Xia, Xiao-hua Zhang, Naohiro Yamaguchi, Martin Morad
Journal: Cardiovascular Research (2023)

Abstract Aims CRISPR/Cas9 gene edits of cardiac ryanodine receptor (RyR2) in human-induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) provide a novel platform for introducing mutations in RyR2 Ca2+-binding residues and examining the resulting excitation contraction (EC)-coupling remodelling consequences. Methods and results Ca2+-signalling phenotypes of mutations in RyR2 Ca2+-binding site residues associated with cardiac arrhythmia (RyR2-Q3925E) or not proven to cause cardiac pathology (RyR2-E3848A) were determined using ICa- and caffeine-triggered Ca2+ releases in voltage-clamped and total internal reflection fluorescence-imaged wild type and mutant cardiomyocytes infected with sarcoplasmic reticulum (SR)-targeted ER-GCaMP6 probe. (i) ICa- and caffeine-triggered Fura-2 or ER-GCaMP6 signals were suppressed, even when ICa was significantly enhanced in Q3925E and E3848A mutant cardiomyocytes; (ii) spontaneous beating (Fura-2 Ca2+ transients) persisted in mutant cells without the SR-release signals; (iii) while 5–20 mM caffeine failed to trigger Ca2+-release in voltage-clamped mutant cells, only ∼20% to ∼70% of intact myocytes responded respectively to caffeine; (iv) and 20 mM caffeine transients, however, activated slowly, were delayed, and variably suppressed by 2-APB, FCCP, or ruthenium red. Conclusion Mutating RyR2 Ca2+-binding residues, irrespective of their reported pathogenesis, suppressed both ICa- and caffeine-triggered Ca2+ releases, suggesting interaction between Ca2+- and caffeine-binding sites. Enhanced transmembrane calcium influx and remodelling of EC-coupling pathways may underlie the persistence of spontaneous beating in Ca2+-induced Ca2+ release-suppressed mutant myocytes.
Acute myeloid leukemias with <i>UBTF</i> tandem duplications are sensitive to menin inhibitors
Authors: Juan M. Barajas, Milad Rasouli, Masayuki Umeda, Ryan Hiltenbrand, Sherif Abdelhamed, Rebecca Mohnani, Bright Arthur, Tamara Westover, Melvin E. Thomas, Minoo Ashtiani, Laura J. Janke, Beisi Xu, Ti-Cheng Chang, Wojciech Rosikiewicz, Emily Xiong, Chandra Rolle, Jonathan Low, Reethu Krishan, Guangchun Song, Michael P. Walsh, Jing Ma, Jeffrey E. Rubnitz, Ilaria Iacobucci, Taosheng Chen, Anja Krippner-Heidenreich, Christian M. Zwaan, Olaf Heidenreich, Jeffery M. Klco
Journal: Blood (2023)

Abstract UBTF tandem duplications (UBTF-TDs) have recently emerged as a recurrent alteration in pediatric and adult acute myeloid leukemia (AML). UBTF-TD leukemias are characterized by a poor response to conventional chemotherapy and a transcriptional signature that mirrors NUP98-rearranged and NPM1-mutant AMLs, including HOX-gene dysregulation. However, the mechanism by which UBTF-TD drives leukemogenesis remains unknown. In this study, we investigated the genomic occupancy of UBTF-TD in transformed cord blood CD34+ cells and patient-derived xenograft models. We found that UBTF-TD protein maintained genomic occupancy at ribosomal DNA loci while also occupying genomic targets commonly dysregulated in UBTF-TD myeloid malignancies, such as the HOXA/HOXB gene clusters and MEIS1. These data suggest that UBTF-TD is a gain-of-function alteration that results in mislocalization to genomic loci dysregulated in UBTF-TD leukemias. UBTF-TD also co-occupies key genomic loci with KMT2A and menin, which are known to be key partners involved in HOX-dysregulated leukemias. Using a protein degradation system, we showed that stemness, proliferation, and transcriptional signatures are dependent on sustained UBTF-TD localization to chromatin. Finally, we demonstrate that primary cells from UBTF-TD leukemias are sensitive to the menin inhibitor SNDX-5613, resulting in markedly reduced in vitro and in vivo tumor growth, myeloid differentiation, and abrogation of the UBTF-TD leukemic expression signature. These findings provide a viable therapeutic strategy for patients with this high-risk AML subtype.
Tuning Blood–Material Interactions to Generate Versatile Hemostatic Powders and Gels
Authors: Xueru Wang, Kai Yuan, Yang Su, Xiaoyue Li, Limin Meng, Nana Zhao, Yang Hu, Feng Duan, Fu‐Jian Xu
Journal: Advanced Healthcare Materials (2023)

Polymer-based hemostatic materials/devices have been increasingly exploited for versatile clinical scenarios, while there is an urgent need to reveal the rational design/facile approach for procoagulant surfaces through regulating blood-material interactions. In this work, degradable powders (PLPS) and thermoresponsive gels (F127-PLPS) are readily developed as promising hemostatic materials for versatile clinical applications, through tuning blood-material interactions with optimized grafting of cationic polylysine: the former is facilely prepared by conjugating polylysine onto porous starch particle, while F127-PLPS is prepared by the simple mixture of PLPS and commercial thermosensitive polymer. In vitro and in vivo results demonstrate that PLPS2 with the optimal-/medium content of polylysine grafts achieve the superior hemostatic performance. The underlying procoagulant mechanism of PLPS2 surface is revealed as the selective fibrinogen adsorption among the competitive plasma-protein-adsorption process, which is the foundation of other blood-material interactions. Moreover, in vitro results confirm the achieved procoagulant surface of F127-PLPS through optimal PLPS2 loading. Together with the tunable thermoresponsiveness, F127-PLPS exhibits outstanding hemostatic utilization in both femoral-artery-injury and renal-artery-embolization models. The work thereby pioneers an appealing approach for generating versatile polymer-based hemostatic materials/devices.
Ikaros is a principal regulator of Aire <sup>+</sup> mTEC homeostasis, thymic mimetic cell diversity, and central tolerance
Authors: Jun Hyung Sin, Juliana Sucharov, Sujit Kashyap, Yi Wang, Irina Proekt, Xian Liu, Audrey V. Parent, Alexander Gupta, Philippe Kastner, Susan Chan, James M. Gardner, Vasilis Ntranos, Corey N. Miller, Mark S. Anderson, Hilde Schjerven, Michael R. Waterfield
Journal: Science Immunology (2023)

Mutations in the gene encoding the zinc-finger transcription factor Ikaros (
Disparity dashboards: an evaluation of the literature and framework for health equity improvement
Authors: Jack Gallifant, Emmett Alexander Kistler, Luis Filipe Nakayama, Chloe Zera, Sunil Kripalani, Adelline Ntatin, Leonor Fernandez, David Bates, Irene Dankwa-Mullan, Leo Anthony Celi
Journal: The Lancet Digital Health (2023)

The growing recognition of differences in health outcomes across populations has led to a slow but increasing shift towards transparent reporting of patient outcomes. In addition, pay-for-equity initiatives, such as those proposed by the Centers for Medicare and Medicaid, will require the reporting of health outcomes across subgroups over time. Dashboards offer one means of visualising data in the health-care context that can highlight essential disparities in clinical outcomes, guide targeted quality-improvement efforts, and ultimately improve health equity. In this Viewpoint, we evaluate all studies that have reported the successful development of a disparity dashboard and share the data collected and unintended consequences reported. We propose a framework for systematic equality improvement through incentivisation of the collecting and reporting of health data and through implementation of reward systems to reduce health disparities.
Supplemental magnetic resonance imaging plus mammography compared with magnetic resonance imaging or mammography by extent of breast density
Authors: Karla Kerlikowske, Weiwei Zhu, Yu-Ru Su, Brian L Sprague, Natasha K Stout, Tracy Onega, Ellen S O’Meara, Louise M Henderson, Anna N A Tosteson, Karen Wernli, Diana L Miglioretti
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Examining screening outcomes by breast density for breast magnetic resonance imaging (MRI) with or without mammography could inform discussions about supplemental MRI in women with dense breasts. Methods We evaluated 52 237 women aged 40-79 years who underwent 2611 screening MRIs alone and 6518 supplemental MRI plus mammography pairs propensity score–matched to 65 810 screening mammograms. Rates per 1000 examinations of interval, advanced, and screen-detected early stage invasive cancers and false-positive recall and biopsy recommendation were estimated by breast density (nondense = almost entirely fatty or scattered fibroglandular densities; dense = heterogeneously/extremely dense) adjusting for registry, examination year, age, race and ethnicity, family history of breast cancer, and prior breast biopsy. Results Screen-detected early stage cancer rates were statistically higher for MRI plus mammography vs mammography for nondense (9.3 vs 2.9; difference = 6.4, 95% confidence interval [CI] = 2.5 to 10.3) and dense (7.5 vs 3.5; difference = 4.0, 95% CI = 1.4 to 6.7) breasts and for MRI vs MRI plus mammography for dense breasts (19.2 vs 7.5; difference = 11.7, 95% CI = 4.6 to 18.8). Interval rates were not statistically different for MRI plus mammography vs mammography for nondense (0.8 vs 0.5; difference = 0.4, 95% CI = -0.8 to 1.6) or dense breasts (1.5 vs 1.4; difference = 0.0, 95% CI = -1.2 to 1.3), nor were advanced cancer rates. Interval rates were not statistically different for MRI vs MRI plus mammography for nondense (2.6 vs 0.8; difference = 1.8 (95% CI = -2.0 to 5.5) or dense breasts (0.6 vs 1.5; difference = -0.9, 95% CI = -2.5 to 0.7), nor were advanced cancer rates. False-positive recall and biopsy recommendation rates were statistically higher for MRI groups than mammography alone. Conclusion MRI screening with or without mammography increased rates of screen-detected early stage cancer and false-positives for women with dense breasts without a concomitant decrease in advanced or interval cancers.
Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression
Authors: Kie Kyon Huang, Haoran Ma, Roxanne Hui Heng Chong, Tomoyuki Uchihara, Benedict Shi Xiang Lian, Feng Zhu, Taotao Sheng, Supriya Srivastava, Su Ting Tay, Raghav Sundar, Angie Lay Keng Tan, Xuewen Ong, Minghui Lee, Shamaine Wei Ting Ho, Tom Lesluyes, Hassan Ashktorab, Duane Smoot, Peter Van Loo, Joy Shijia Chua, Kalpana Ramnarayanan, Louis Ho Shing Lau, Takuji Gotoda, Hyun Soo Kim, Tiing Leong Ang, Christopher Khor, Jonathan Wei Jie Lee, Stephen Kin Kwok Tsao, Wei Lyn Yang, Ming Teh, Hyunsoo Chung, Jimmy Bok Yan So, Khay Guan Yeoh, Patrick Tan
Journal: Cancer Cell (2023)

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to transform to GC. By highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression, our results raise opportunities for GC precision prevention and interception.
Thrombin and Thrombin‐Incorporated Biomaterials for Disease Treatments
Authors: Qiong‐Dan Zhang, Qiu‐Yi Duan, Jing Tu, Fu‐Gen Wu
Journal: Advanced Healthcare Materials (2023)

Thrombin, a coagulation-inducing protease, has long been used in the hemostatic field. During the past decades, many other therapeutic uses of thrombin have been developed. For instance, burn treatment, pseudoaneurysm therapy, wound management, and tumor vascular infarction (or tumor vasculature blockade therapy) can all utilize the unique and powerful function of thrombin. Based on their therapeutic effects, many thrombin-associated products have been certificated by the Food and Drug Administration, including bovine thrombin, human thrombin, recombinant thrombin, fibrin glue, etc. Besides, several thrombin-based drugs are currently undergoing clinical trials. In this article, the therapeutic uses of thrombin (from the initial hemostasis to the latest cancer therapy), the commercially available drugs associated with thrombin, and the pros and cons of thrombin-based therapeutics (e.g., adverse immune responses related to bovine thrombin, thromboinflammation, and vasculogenic "rebounds") are summarized. Further, the current challenges and possible future research directions of thrombin-incorporated biomaterials and therapies are discussed. It is hoped that this review may provide a valuable reference for researchers in this field and help them to design safer and more effective thrombin-based drugs for fighting against various intractable diseases.
Elexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events
Authors: Bonnie Ramsey, Christoph U. Correll, David R. DeMaso, Edward McKone, Elizabeth Tullis, Jennifer L. Taylor-Cousar, Chenghao Chu, Nataliya Volkova, Neil Ahluwalia, David Waltz, Simon Tian, Marcus A. Mall
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (pwCF) aged 2 years and older with at least one
Advances in molecular pathology, diagnosis, and treatment of amyotrophic lateral sclerosis
Authors: Hristelina Ilieva, Mithila Vullaganti, Justin Kwan
Journal: BMJ (2023)

Abstract Although the past two decades have produced exciting discoveries in the genetics and pathology of amyotrophic lateral sclerosis (ALS), progress in developing an effective therapy remains slow. This review summarizes the critical discoveries and outlines the advances in disease characterization, diagnosis, imaging, and biomarkers, along with the current status of approaches to ALS care and treatment. Additional knowledge of the factors driving disease progression and heterogeneity will hopefully soon transform the care for patients with ALS into an individualized, multi-prong approach able to prevent disease progression sufficiently to allow for a dignified life with limited disability.
A commentary on “incidence, risk factors, and outcomes of venous thromboembolism in patients undergoing surgery for retroperitoneal tumors: a propensity-matched retrospective cohort study”.
Authors: Gang Wang, Ning Zhuo, Liu Zhichun
Journal: International Journal of Surgery (2023)

aDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China bDepartment of Nephrology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, China GANG WANG (Orcid ID: 0000-0002-8836-1593) Article type: Letter to the editor Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou, China, Tel:86-51267784169. E-mail address: [email protected] (Z. Liu). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/